Metabolic syndrome: an Asian perspective

Source: International Chair on Cardiometabolic Riskwww.cardiometabolic-risk.org

Metabolic Syndrome: An Asian Perspective

Juliana C N Chan MBChB, MD, FRCP

Professor of Medicine & Therapeutics Director, Hong Kong Institute of Diabetes and Obesity

The Chinese University of Hong KongHong Kong, China

Source: International Chair on Cardiometabolic Risk www.cardiometabolic-risk.org

General Outline

Obesity and metabolic syndrome – a public health

perspective

Ethnicity, obesity and cardio-renal complications

Hormonal dysregulation in metabolic syndrome

Genetics of a multifaceted syndrome

Emerging role of mesenteric fat as the linking factor

Power of weight reduction on risk profiles

The way forward – from risk stratification to structured

care


http://www.who.int/chp/chronic_disease_report/en/index.html

Economic and humanistic burden of chronic diseases


Common risk factors for chronic diseases

Deaths from 4 chronic diseases

Deaths from all other causes

50% of all deaths

3 risk factors

Tobacco Poor diet Lack of exercice

4 chronic diseases

CancerType 2 diabetesChronic respiratory

diseaseCardiovascular

Oxford Health Alliance 2003


Same Body Mass Index, Higher Risk for Diabetes in Asians

Adapted from Yoon KH et al. Lancet 2006; 368: 1681-8Reproduced with permission

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1970-1989

1990-2005Obesity

Overweight

Pre

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%)

Pre

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<20 20-21.9

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26-27.9

28-29.9

30

% of Asian Population Having at Least One Risk Factor Stratified by Body Mass Index

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MenWomenPhilippines

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Adapted from Lancet WHO expert consultation 2004; 363: 157-63Reproduced with permission

Body mass index (kg/m2)

Pop

ulat

ion

with

>1

risk

fact

or

(%)


Obesity, Type 2 Diabetes, Hypertension or Dyslipidemia

Rel

ativ

e ri

sk

Waist circumference (cm)

Adapted from Lee ZSK et al. Obes Rev 2002; 3: 173-82 andKo GT et al. Int J Obes Relat Metab Disord 1997; 21: 995-1001

0


Prediction of Intra-abdominal (Visceral) Obesity from Body Mass Index, Waist Circumference and Waist-to-Hip Ratio in Chinese Adults

From Jia WP et al. Biomed Environ Sci 2003; 16: 206-11Reproduced with permission

Receiver Operating Characteristics (ROC) curves analysis

ROC curves of BMI, WC and WHR for the determination of abdominal visceral obesity (≥ 100 cm2)

BMI: body mass indexWC: waist circumferenceWHR: waist-to-hip ratio


Comparisons of Body Mass Index Between Patients with Increasing Number of Morbidity Condition(s)

Bod

y m

ass

inde

x (k

g/m

2 )

Adapted from Lee ZSK et al. Obes Rev 2002; 3: 173-82

Number of morbidity condition(s)

Type 2 diabetes Hypertension Dyslipidemia

0 1 2 0 1 2 0 1 2

Morbidity conditions included type 2 diabetes, hypertension, dyslipidemia and albuminuria


Comparisons of Waist Circumference Between Patients with Increasing Number of Morbidity Condition(s)

Wai

st c

ircum

fere

nce

(cm

)

Number of morbidity conditions

Type 2 diabetes Hypertension Dyslipidemia

Adapted from Lee ZSK et al. Obes Rev 2002; 3: 173-82

Morbidity conditions included type 2 diabetes, hypertension, dyslipidemia and albuminuria

Number of morbidity condition(s)

0 1 2 0 1 2 0 1 2


Additive Odds Ratios of Waist Circumference (WC) and Body Mass Index (BMI) on Cardiometabolic Risk Factors in 2,895 Hong Kong Chinese

Adapted from Thomas GN et al. Obes Res 2004; 12: 1805-13Reprinted by permission from Macmillan Publishers Ltd, © 2004

† Adjusted for WC‡ Adjusted for BMI

* Adjusted for gender

BMI† Quartile 1 Quartile 2 Quartile 3 Quartile 4

Hypertension 1.0 1.2 (0.8 to 1.8) 1.5 (0.9 to 2.3) 2.7 (1.6 to 4.6)

Dyslipidemia 1.0 1.5 (1.1 to 2.0) 1.8 (1.3 to 2.5) 2.2 (1.4 to 3.2)

Diabetes 1.0 1.3 (0.9 to 1.8) 1.8 (1.2 to 2.5) 2.0 (1.3 to 3.0)

WC‡ Quartile 1 Quartile 2 Quartile 3 Quartile 4



Diabetes 1.0 1.1 (0.8 to 1.6) 2.2 (1.5 to 3.3) 3.6 (2.2 to 5.7)

Obesity types*

NonobeseBMI obese

aloneWaist obese

aloneBMI and waist

obese



Diabetes 1.0 2.2 (1.7 to 2.9) 3.2 (2.0 to 5.2) 3.9 (3.1 to 4.8)

Quartile ranges for BMI are: (1) 14.78-20.56, (2) 20.57-22.10, (3) 22.11-23.52, and (4) 23.53-25.00 kg/m2 Quartile ranges for WC are: (1) 49.8-68.0, (2) 68.3-73.1, (3) 73.3-78.3, and (4) 78.5-89.8 cm


Metabolic Syndrome – A Multifaceted Syndrome

High blood glucose

Highblood

pressure

Abnormal lipid levels

Obesity

Heart diseaseStroke

Kidney failure Depression?

Cancer?

Urine protein

Inflammatory markers


Predictors for Diabetes in US Japanese Men

Variables OR (95% CI) P value

Age 1.4 (1.0 – 2.0) 0.065

Female gender 1.8 (0.8 – 4.2) 0.176

IGT at baseline 4.5 (2.3 – 9.0) <0.001

Family history of diabetes 1.9 (1.0 – 3.3) 0.040

Intra-abdominal (visceral) fat 1.6 (1.1 – 2.4) 0.023

Body mass index 0.8 (0.5 – 1.2) 0.251

Fasting C-peptide 1.4 (1.1 – 1.8) 0.016

Incremental insulin response 0.5 (0.3 – 0.9) 0.022

Adapted from Boyko EJ et al. Diabetes Care 2000; 23: 465-71

IGT: impaired glucose toleranceOR: odds ratio


Intra-abdominal (Visceral) Fat and Coronary Heart Disease (CHD) in Japanese

Incident CHD status

Baseline variables CHD absent CHD present P value P value*

n 125 50 _ _

Weight (kg) 69.8 0.9 71.6 1.2 0.25 0.24

Body mass index (kg/m2) 25.4 0.3 25.8 0.4 0.37 0.34

Computed tomography fat area (cm2)

Total 417.1 14.0 465.9 20.8 0.063 0.052

Chest subcutaneous 92.7 4.1 104.0 5.6 0.13 0.14

Abdomen subcutaneous 129.3 5.7 146 7.9 0.11 0.068

Intra-abdominal (visceral) 108.9 4.7 133.0 7.6 0.0075 0.016

Left thigh subcutaneous 43.1 1.5 40.8 2.1 0.39 0.72

Adapted from Fujimoto WY et al. Diabetes Care 1999; 22: 1808-12

*Adjusted for baseline diabetes


Predictors for Coronary Heart Disease in US Japanese Men

Variables (1 SD) OR (95% CI) P value

Intra-abdominal (visceral) fat area 1.7 (1.11-2.23) 0.009

Fasting glucose 1.91 (1.36-2.68) 0.0002

2-hour glucose 1.73 (1.25-2.4) 0.008

HDL cholesterol 0.60 (0.44-0.88) 0.0086

HDL2 cholesterol 0.65 (0.44-0.87) 0.03

HDL3 cholesterol 0.65 (0.46-0.94) 0.018

Fasting triglycerides 1.56 (1.09-2.13) 0.013

Systolic blood pressure 1.83 (1.28-2.6) 0.0007

Diastolic blood pressure 2.05 (1.4-3.1) 0.002

After adjustment for age, sex and body mass index

Adapted from Fujimoto WY et al. Diabetes Care 1999; 22: 1808-12


Metabolic Syndrome and Chronic Kidney Disease

Adapted from Chen J et al. Ann Intern Med 2004; 140: 167-74

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25P

reva

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Metabolic syndrome risk factors

Chronic kidney disease

Microalbuminuria


Glomerular Filtration Rate (GFR) Predicts All-cause Mortality, Cardiovascular and Renal Endpoints in 4,421 Chinese Type 2 Diabetic Patients (3.5-year Follow-up)

Adapted from So WY et al. Diabetes Care 2006; 29: 2046-52

Time (months)

7260483624120

Cum

ulat

ive

com

posite

eve

nts

1.0

.8

.6

.4

.2

0.0

Estimated GFR

15-29

30-59

60-89

>=90


TG and HDL cholesterol

ß cell function

BG

Adipocytokines & FFA

Insulin resistance

CVS and renal complications

Metabolic Syndrome - A Unifying Hypothesis

AgingFamily history(Genetics or

shared environment)

Psychosocialstress

Visceral fatGH and IGF-1

Testosterone (M)Testosterone (F)

Cortisol

SNS

RAAS BP

Activated immunity

Adapted from Björntorp P. Obes Res 1993; 1: 206-22 and Chan JCN et al. Diabetes Care 1995; 18: 1013-6. Luk A and Chan JCN Diabetes Res Clin Pract 2008: 82 Suppl 1:S15-20


Age, Family History of Diabetes and Obesity are Major Explanatory Variables of Metabolic Syndrome in Hong Kong Chinese

Male model Female model

*p<0.05Copyright © 1999 American Diabetes AssociationAdapted from Diabetes Care ®, Vol. 19, 1996; 953-9Reprinted with permission from The American Diabetes Association


Growth Hormone (GH) and Cortisol in Young Patients with Type 2 Diabetes

Pla

sma

GH

(ng

/ml)

Pla

sma

cort

iso

l(n

mo

l/l)

Pla

sma

insu

lin(p

mo

l/l) Controls (n=104)

Type 2 diabetics (n=90)

Copyright © 1999 American Diabetes AssociationAdapted from Diabetes Care ®, Vol. 22, 1999; 1450-7Reprinted with permission from The American Diabetes Association


Mea

n D

BP

(m

mH

g)

Clock time (hours)

Intra-abdominal (Visceral) Fat Area Tertiles and 24-hour Ambulatory Blood Pressure and Pulse Rate in Chinese Type 2 Diabetic Patients

Clock time (hours)

Mea

n H

R (

bp

m)

Clock time (hours)

Mea

n S

BP

(m

mH

g)

DBP: diastolic blood pressureHR: heart rateSBP: systolic blood pressure

Copyright © 1997 American Diabetes AssociationAdapted from Diabetes Care ®, Vol. 20, 1997; 1854-8Reprinted with permission from The American Diabetes Association


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1.0

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Quartile 158-67

Quartile 268-74

Quartile 375-84

Quartile 485-123

Central Obesity, Insulin Cortisol, Growth Hormone and 24-hour Urinary Catecholamines in 100 Young Type 2 Diabetic Patients and 90 Control Subjects

Waist circumference (cm) Dates are expressed as * geometric means and ** means

Adapted from Lee ZSK et al. Diabetes Care 1999; 22: 1450-7 and Lee ZSK et al. Metabolism 2001; 50: 135-43

Insulin*p for the trend <0.001

Growth hormonep for the trend <0.05

Cortisol*p for the trend <0.01

pmol

/lng

/ml

nmol

/l

nmol

/day

Quartile 158-67

Quartile 268-74

Quartile 485-123

Quartile 375-84

Noradrenaline*p for the trend <0.01

Adrenaline*p for the trend <0.001

Waist circumference (cm)


Insulin-like Growth Factor-1 (IGF-1), High Sensitivity C-Reactive Protein (hs-CRP), Testosterone and Metabolic Syndrome in Chinese Men

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Adapted from Tong PCY et al. J Clin Endocrinol Metab 2005; 90: 6418-23Reproduced with permissionCopyright 2005, The Endocrine Society

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Multipoint Linkage Analyses for Metabolic Syndrome-related Quantitative Traits in 178 Families

Copyright © 2004 American Diabetes AssociationAdapted from Diabetes®, Vol. 53, 2004; 2676-83Reprinted with permission from The American Diabetes Association

The horizontal axis is cM from p-terminus


Major gene(s) for metabolic syndrome in chromosome 1q

Multipoint Linkage Analyses on Chromosomes 1, 2 and 16 for Metabolic Syndrome and its Component in 53 Families

Copyright © 2004 American Diabetes AssociationAdapted from Diabetes®, Vol. 53, 2004; 2676-83Reprinted with permission from The American Diabetes Association

The number of affected relative pairs included in each analysis is indicated in parenthesesThe horizontal axis is cM from p-terminus


Are All Fat Depots the Same?

Correlation between intra-abdominal (visceral) fat volume and mesenteric fat = 0.8

From Liu KH et al. Int J Obes Relat Metab Disord 2003; 27: 1267-73Reproduced with permission

Figure - Ultrasonogram of mesenteric leaves. Each mesenteric leaf is indicated by highly reflecting peritoneal surfaces (arrows). The maximum mesenteric thickness on the image was measured with the calipers (+).


Predictors of Fatty Liver in Chinese Men

Variables Odds ratio (95% CI) P value

Model 1

Mesenteric fat thickness 1.50 (1.27-1.77) <0.001

Triglycerides 2.64 (1.40-4.99) 0.003

HOMA 1.06 (1.00-1.12) 0.036

Model 2

Mesenteric fat thickness 1.34 (1.12-1.60) 0.002

Triglycerides 2.35 (1.19-4.63) 0.013

Body mass index 1.51 (1.26-1.82) <0.001

Adapted from Liu KH et al. Int J Obes Relat Metab Disord 2006; 30: 787-93


±SE P value Odds ratio (95% Cl)

Mesenteric fat thickness

0.30 ± 0.11 0.004 1.35 (1.10-1.66)

Preperitoneal fat thickness

-0.058 ± 0.07 0.41 0.94 (0.82-1.08)

Subcutaneous fat thickness

0.01 ± 0.034 0.77 1.01 (0.95-1.08)

HOMA-IR 0.33 ± 0.17 0.059 1.05 (1.00-1.10)

Sex 0.088 ± 0.61 0.885 1.09 (0.28-3.02)

Age 0.01 ± 0.034 0.775 1.01 (0.94-1.08)

Using receiver-operating characteristic curve analysis, the cutoff value of 10 mm of mesenteric fat thickness had 70% sensitivity and 75% specificity to predict metabolic syndrome

Multivariate Logistic Regression Analysis to Identify Independent Determinant(s) of the Metabolic Syndrome in 290 Chinese Apparently Healthy Subjects

Adapted from Liu KH et al. Diabetes Care 2006; 29: 379-84

: regression coefficientSE: standard error


Mesenteric Fat Thickness and Carotid Intima-Media Thickness (IMT)

0.58

0.60

0.62

0.64

0.66

0.68

0.70

0.72

0.74

Car

otid

IMT

(m

m)

Adapted from Liu KH et al. Diabetes Care 2006; 29: 379-84

From Liu KH et al. Atherosclerosis 2005; 179:299-304Reproduced with permission

Mesenteric fat≥10 mm Mesenteric fat<10 mm


Structured Weight Management Program and Waist Circumference

% C

han

ge

in w

aist

cir

cum

fere

nce

Months of anti-obesity drug

Obese patients with type 2 diabetes

Obese patients without diabetes

Adapted from Tong PCY et al. Arch Intern Med 2002; 162: 2428-35Reproduced with permissionCopyright © 2002, American Medical Association. All rights reserved.


Insulin Resistance Index (HOMA-IR) Between Baseline and End of 6-month Weight Management Program

- 11.7 %

- 19.5 %

0

25

50

75

100

125

Baseline Month 6

p=0.006

Obese patients with

type 2 diabetes

Baseline Month 6

p=0.026

HO

MA

-IR

Obese patients without diabetes

Adapted from Tong PCY et al. Arch Intern Med 2002; 162: 2428-35


Change in Risk Factors after 6 Months of Weight Management Program in Hong Kong Chinese

-20

-18

-16

-14

-12

-10

-8

-6

-4

-2

0

Diabetics

Nondiabetics% c

han

ge

BMI: body mass index FPG: fasting plasma glucose FPI: fasting plasma insulin HbA1c: glycosylated hemoglobin

Adapted from Tong PCY et al. Arch Intern Med 2002; 162: 2428-35

BMI WC Body fat FPG TGHbA1c SBP FPI

SBP: systolic blood pressureTG: triglyceridesWC: waist circumference


A Holistic View of Obesity and Diabetes

Genes

Environment

Psycho-socio-cognitive-behavioral changese.g. overeating, physical withdrawal, slow learning,

depression, socioeconomical deprivation…

Adaptation through education

Improved clinical outcomes

Disease state


Obese subjects (30% of population)

Diabetic patients (10% of population)

Risk stratification program

Weight management program

(lifestyle ± medication)

Diabetes comprehensivecare program

(self care ± medication)

Treat to Target and Stay on Target


Conclusion

Obesity, diabetes and metabolic syndrome are running rampant in Asia

Asians develop cardiometabolic risk factors at a considerably lower body mass index and waist circumference values

Obesity is a major predictor for cardio-renal complications in Asian population

Genetics, age and stress-related hormonal changes causing obesity may be particularly relevant to Asian populations

Risk stratification and structured program reduce obesity and associated risk factors in Chinese population


www.cardiometabolic-risk.org

Metabolic syndrome: an Asian perspective

Health & Medicine

Transcript of Metabolic syndrome: an Asian perspective